Identification and characterization of a novel anti-inflammatory lipid isolated from Mycobacterium vaccae, a soil-derived bacterium with immunoregulatory and stress resilience properties
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Department of Pathology, Anatomy, and Cellular Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA. email@example.com.
- Merck Research Laboratories, MSD, Kenilworth, NJ, USA.
- School of Bioscience, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér, 1, Debrecen, 4032, Hungary.
- BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.
- Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO, 80309, USA.
- Department of Medicine, Johns Hopkins University, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, 33701, USA.
- University College London
- inVIVO Planetary Health, of the Worldwide Universities Network (WUN), West New York, NJ, 07093, USA. firstname.lastname@example.org.
RATIONALE: Mycobacterium vaccae (NCTC 11659) is an environmental saprophytic bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties. Previous studies have shown that whole, heat-killed preparations of M. vaccae prevent allergic airway inflammation in a murine model of allergic asthma. Recent studies also demonstrate that immunization with M. vaccae prevents stress-induced exaggeration of proinflammatory cytokine secretion from mesenteric lymph node cells stimulated ex vivo, prevents stress-induced exaggeration of chemically induced colitis in a model of inflammatory bowel disease, and prevents stress-induced anxiety-like defensive behavioral responses. Furthermore, immunization with M. vaccae induces anti-inflammatory responses in the brain and prevents stress-induced exaggeration of microglial priming. However, the molecular mechanisms underlying anti-inflammatory effects of M. vaccae are not known.
OBJECTIVES: Our objective was to identify and characterize novel anti-inflammatory molecules from M. vaccae NCTC 11659.
METHODS: We have purified and identified a unique anti-inflammatory triglyceride, 1,2,3-tri [Z-10-hexadecenoyl] glycerol, from M. vaccae and evaluated its effects in freshly isolated murine peritoneal macrophages.
RESULTS: The free fatty acid form of 1,2,3-tri [Z-10-hexadecenoyl] glycerol, 10(Z)-hexadecenoic acid, decreased lipopolysaccharide-stimulated secretion of the proinflammatory cytokine IL-6 ex vivo. Meanwhile, next-generation RNA sequencing revealed that pretreatment with 10(Z)-hexadecenoic acid upregulated genes associated with peroxisome proliferator-activated receptor alpha (PPARα) signaling in lipopolysaccharide-stimulated macrophages, in association with a broad transcriptional repression of inflammatory markers. We confirmed using luciferase-based transfection assays that 10(Z)-hexadecenoic acid activated PPARα signaling, but not PPARγ, PPARδ, or retinoic acid receptor (RAR) α signaling. The effects of 10(Z)-hexadecenoic acid on lipopolysaccharide-stimulated secretion of IL-6 were prevented by PPARα antagonists and absent in PPARα-deficient mice.
CONCLUSION: Future studies should evaluate the effects of 10(Z)-hexadecenoic acid on stress-induced exaggeration of peripheral inflammatory signaling, central neuroinflammatory signaling, and anxiety- and fear-related defensive behavioral responses.
|Number of pages||18|
|Early online date||22 May 2019|
|Publication status||E-pub ahead of print - 22 May 2019|
- 10(Z)-hexadecenoic acid, Bacteria, Inflammation, Interleukin 6, Lipid, Macrophage, Mycobacteria, PPAR, RNA-seq, vaccae